m6A-centered Disease Response Information

General Information of the Disease (ID: M6ADIS0159)

Name	Injury of heart
ICD	ICD-11: NB31

Full List of Target Gene(s) of This m6A-centered Disease Response

miR-503

Target Info

In total 1 item(s) under this target gene
Experiment 1 Reporting the m6A-centered Disease Response by This Target Gene			[5]
Response Summary	Hypoxia induced rapid H3K4 methylation of the promoter of the methyltransferase-like 3 gene (METTL3) and resulted in its overexpression. METTL3 overexpression evokes N6-methyladenosine (m6A)-dependent miR-503 biogenesis in endothelial cells. In summary, this study highlights a novel endogenous mechanism wherein EVs aggravate myocardial injury during the onset of AMI via endothelial cell-secreted miR-503 shuttling.
Responsed Disease	Myocardial injury [ICD-11: NB31.Z]
Target Regulator	Methyltransferase-like 3 (METTL3)	WRITER	Regulator Info
Target Regulation	Up regulation
Cell Process	Mitochondrial metabolic dysfunction
In-vivo Model	To generate an AMI mouse model, mice were anesthetised by intraperitoneal injection of sterile pentobarbital sodium at 50 mg/kg body weight.

Full List of Crosstalk(s) between m6A Modification and Epigenetic Regulation Related to This Disease

In total 3 item(s) under this disease
Crosstalk ID: M6ACROT03071		Crosstalk Info
m6A Regulator	Methyltransferase-like 3 (METTL3)	Regulator Info
m6A Target	miR-503	Target Gene
Epigenetic Regulator	Histone-lysine N-methyltransferase 2A (KMT2A)
Regulated Target	Histone H3 lysine 4 trimethylation (H3K4me3)
Crosstalk relationship	Histone modification → m6A
Drug	C646	Drug Info
Crosstalk ID: M6ACROT05154		Crosstalk Info
m6A Regulator	RNA demethylase ALKBH5 (ALKBH5)	Regulator Info
m6A Target	NAD-dependent protein deacetylase sirtuin-1 (SIRT1)	Target Gene
Epigenetic Regulator	hsa-miR-193a-3p
Regulated Target	RNA demethylase ALKBH5 (ALKBH5)
Crosstalk relationship	ncRNA → m6A
Drug	Suxiao Jiuxin Pill	Drug Info
Crosstalk ID: M6ACROT05626		Crosstalk Info
m6A Regulator	Methyltransferase-like 3 (METTL3)	Regulator Info
m6A Target	miR-503	Target Gene
Epigenetic Regulator	MiR-503
Regulated Target	PPARG coactivator 1 beta (PPARGC1B)
Crosstalk relationship	m6A → ncRNA

References

Ref 1	Comparison of the safety, tolerability, and pharmacokinetic profile of a single oral dose of pitavastatin 4 mg in adult subjects with severe renal impairment not on hemodialysis versus healthy adult subjects. J Cardiovasc Pharmacol. 2012 Jul;60(1):42-8. doi: 10.1097/FJC.0b013e318256cdf0.
Ref 2	Broad spectrum matrix metalloproteinase inhibitors: an examination of succinamide hydroxamate inhibitors with P1 C alpha gem-disubstitution. Bioorg Med Chem Lett. 1998 Jun 16;8(12):1443-8. doi: 10.1016/s0960-894x(98)00255-8.
Ref 3	Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)?. J Autoimmun. 2020 Jul;111:102452. doi: 10.1016/j.jaut.2020.102452. Epub 2020 Apr 10.
Ref 4	Clinical pipeline report, company report or official report of LipimetiX.
Ref 5	Extracellular vesicle-packaged mitochondrial disturbing miRNA exacerbates cardiac injury during acute myocardial infarction. Clin Transl Med. 2022 Apr;12(4):e779. doi: 10.1002/ctm2.779.
Ref 6	The Role of Levomilnacipran in the Management of Major Depressive Disorder: A Comprehensive Review. Curr Neuropharmacol. 2016;14(2):191-9. doi: 10.2174/1570159x14666151117122458.